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Updated: Jul 13, 2026

A Protocol for Constructing a Rat Wound Model of Type 1 Diabetes
Published on: February 17, 2023
Nitric oxide restores impaired healing in normoglycaemic diabetic rats
M Schäffer1, M Bongartz, S Fischer
1I Department of Surgery, University Hospital, Knappschaftskrankenhaus Bochum-Langendreer, Germany. michael.schaeffer@kk-bochum.de
Objective:
Hyperglycaemia impairs wound healing. However, little is known about the underlying cellular mechanisms that lead to diminished wound repair in insulin-controlled and non-insulin-controlled diabetes. This study investigated the role of endogenous and exogenous nitric oxide on incisional wound healing in diabetic rats.
Method:
Groups of 10 wild-typeWistar control rats - 10 genetically diabetic BioBreeding rats and 10 genetically diabetic BioBreeding rats treated with subcutaneous insulin implants to render them normoglycaemic - underwent dorsal skin incision followed by subcutaneous insertion of polyvinyl alcohol sponges. The rats were sacrificed 10 days later to determine the wound-breaking strength and reparative collagen deposition. Nitric oxide, an important mediator in diabetic wound healing and collagen synthesis, was measured in wound fluid. Wound-derived fibroblasts were tested for ex vivo synthesis of nitric oxide and collagen. Exogenous nitric oxide was used for the therapeutic interventions.
Results:
Wound-breaking strength and wound collagen deposition were significantly impaired in the hyperglycaemic diabetic animals (p<0.01). Wound nitric-oxide synthesis and ex vivo wound fibroblast nitric-oxide production were reduced in the hyperglycaemic rats (p<0.01). Insulin treatment partially reversed some of the effects of hyperglycaemia on wound repair (p<0.05). Exogenous nitric oxide further restored wound mechanical strength, collagen deposition and fibroblast collagen synthesis (p<0.01) in insulin-treated (normoglycaemic) diabetic animals.
Conclusion:
Wound healing is impaired in hyperglycaemic and normoglycaemic diabetic rats. This is reflected in impaired wound fibroblast nitric-oxide synthesis. Used in combination with insulin, exogenous nitric oxide further improves healing outcomes, making it a potential target for therapeutic intervention in insulin-treated normoglycaemic diabetes.
Insights
Diabetes impairs wound healing by reducing nitric oxide (NO) synthesis. Supplementing with exogenous NO, alongside insulin, significantly improves wound repair and collagen deposition in diabetic rats.
Area of Science:
- Biomedical Science
- Wound Healing Research
- Diabetes Mellitus Pathophysiology
Background:
- Hyperglycaemia is known to impede wound healing.
- Cellular mechanisms underlying impaired wound repair in diabetes remain incompletely understood.
- The role of nitric oxide (NO) in diabetic wound healing requires further elucidation.
Purpose of the Study:
- To investigate the impact of endogenous and exogenous nitric oxide on incisional wound healing in diabetic rats.
- To compare wound repair in hyperglycaemic, normoglycaemic diabetic, and control rats.
- To assess the therapeutic potential of nitric oxide in diabetic wound management.
Main Methods:
- Utilized three groups of Wistar rats: control, genetically diabetic (BioBreeding), and insulin-treated normoglycaemic diabetic.
- Assessed wound-breaking strength and collagen deposition 10 days post-incision.
- Measured nitric oxide in wound fluid and ex vivo fibroblast nitric oxide/collagen synthesis.
- Administered exogenous nitric oxide as a therapeutic intervention.
Main Results:
- Hyperglycaemic diabetic rats exhibited significantly impaired wound healing, reduced wound breaking strength, and diminished collagen deposition (p<0.01).
- Both wound and fibroblast nitric oxide synthesis were significantly reduced in hyperglycaemic rats (p<0.01).
- Insulin treatment partially improved wound repair (p<0.05), while exogenous nitric oxide further enhanced mechanical strength, collagen deposition, and fibroblast collagen synthesis in insulin-treated diabetic rats (p<0.01).
Conclusions:
- Diabetic rats, both hyperglycaemic and normoglycaemic, show impaired wound healing linked to reduced fibroblast nitric oxide synthesis.
- Exogenous nitric oxide, in conjunction with insulin, demonstrates potential as a therapeutic strategy to improve wound healing outcomes in insulin-treated diabetic individuals.
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